Concussion AF trial: Longitudinal assessment of brain injury biomarkers and cognitive decline in elderly patients with atrial fibrillation

BACKGROUND: Atrial fibrillation (AF) is associated with cognitive impairment. Serum biomarkers to detect subclinical brain injury or predict dementia in patients with anticoagulated AF are understudied. OBJECTIVE: This study aimed to quantify neural injury biomarkers and assess their ability to predict incident dementia or moderate cognitive decline in patients with AF. METHODS: Prospective longitudinal study of 120 patients with AF (mean age 71.1 ± 10.7 years; 62.5% male) without baseline dementia. Assessments at baseline and at 6, 12, and 24 months (60% completed all visits). Cognitive and functional measures included the Mini-Mental State Examination (MMSE), the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog11), the Disability Assessment for Dementia, and quality-of-life measures. Serum biomarkers measured were glial fibrillary acidic protein, neuron-specific enolase (NSE), tau, S100 calcium-binding protein B (S100B), and spectrin N-terminal fragment (SNT145). The primary endpoint was incident dementia (MMSE score <24 with memory-related quality-of-life impact). The secondary endpoint was moderate cognitive decline defined as >30% worsening in ADAS-cog11 or >30% decline in the Disability Assessment for Dementia. RESULTS: Comorbidities were common: hypertension 64.2%, heart failure 23%, diabetes 16%, and sleep apnea 30.8%; 2 had previous stroke. No participants met the criteria for incident dementia; 3 had an MMSE score of <24 without quality-of-life impact. At 24 months, 9 of 72 (12.5%) exhibited moderate cognitive decline by ADAS-cog11. Biomarkers indicated chronic subclinical stress rather than acute injury: S100B was persistently elevated (baseline 0.18 ± 0.23; 24 months 0.18 ± 0.19 pg/mL). SNT145 was elevated (baseline 2.85 ± 3.73; 24 months 2.36 ± 1.86 ng/mL). NSE and tau remained within normal ranges; inflammatory markers were persistently elevated. Changes in biomarker levels did not correlate with cognitive decline. CONCLUSION: Over 2 years, dementia incidence was low but 12.5% experienced moderate cognitive decline. Persistent elevations of S100B and SNT145 suggest ongoing subclinical brain injury in patients with anticoagulated AF without acute spikes in traditional stroke markers such as NSE.